Total syntheses of (-)- and (+)-boronolide and their plant growth-inhibitory activitySatoshi Yamauchi, Satoshi Yamauchi, Yasuyoshi Isozaki, Hiroki Nishimura, Tomoko Tsuda, Hisashi Nishiwaki, Yoshihiro Shuto, Bioscience, Biotechnology and Biochemistry, 76, 2012年10月01日, Optically pure (+)- and (-)-boronolides were stereoselectively synthesized from yeast reductive products which had been obtained by yeast reduction of one common racemic substrate. The lactone structure of boronolide was constructed by Baeyer-Villiger oxidation. The stereochemistry of the yeast reduction products was studied to obtain the stereocenters at 5 positions of the dodecanolides of (+)- and (-)-boronolides. The stereochemistry of the 6 and 7 positions was obtained by AD-mix-α or β oxidation. The chiral center at the 8 position was constructed by employing (R)-(+)- or (S)-(-)-2-methyl-CBS- oxazaborolidine reduction or the Mitsunobu reaction. The plant growth-inhibitory activity against Echinochloa crusgalli L. of naturally occurring (+)-boronolide was higher than that of the (-)-boronolide.

Larvicidal activity of (-)-dihydroguaiaretic acid derivatives against culex pipiensHisashi Nishiwaki, Ayaka Hasebe, Yuya Kawaguchi, Miki Akamatsu, Yoshihiro Shuto, Satoshi Yamauchi, Bioscience, Biotechnology and Biochemistry, 75, 2011年09月, The larvicidal activity against Culex pipiens of all stereoisomers of dihydroguaiaretic acid (DGA) and secoisolariciresinol was measured, and these DGAs were found to be potent. Sixteen (-)-DGA derivatives were then newly synthesized to analyze their structureactivity relationship. Two derivatives monohydroxylated at the 3- or 4-position of the 7-phenyl group of DGA induced acute paralytic activity in the mosquitoes. Derivatives with several hydroxyl groups had lower activity than the natural compound, suggesting that hydrophobicity was probably an important factor for their insecticidal activity.

Syntheses of secocyclolignanes and comparative antioxidative activity between secocyclolignane and the dibenzyl type of lignanMasao Morita, Hisashi Nishiwaki, Yoshimi Shingai, Aya Fujimoto, Toshiya Masuda, Satoshi Yamauchi, Bioscience, Biotechnology and Biochemistry, 75, 2011年06月, The antioxidative activity of secocyclolignanes was compared with that of the corresponding dibenzyl lignans for the first time. The radical scavenging activity of the secocyclolignanes was weaker than that of the corresponding dibenzyl lignans, the butane diol type showing the highest activity. The butane type of secocyclolignane exhibited the highest antioxidant activity of the unsaturated fatty acid.

Immunomodulatory effect of (-)-matairesinol in vivo and ex vivoManami Yamawaki, Kosuke Nishi, Sogo Nishimoto, Satoshi Yamauchi, Koichi Akiyama, Taro Kishida, Masafumi Maruyama, Hisashi Nishiwaki, Takuya Sugahara, Bioscience, Biotechnology and Biochemistry, 75, 2011年06月, Matairesinol is one of the lignan compounds found in a variety of plant foodstuffs. We investigated the immunomodulatory effects of (-)-matairesinol in vivo and ex vivo by using mice. Although we found no significant differences in the IgG, IgA and IgM levels in the serum, the IgE level was strongly suppressed by the uptake of (-)-matairesinol in both intact and ovalbumin-immunized mice. The immunoglobulin produced by lymphocytes from the spleen was not activated by the intake of (-)-matairesinol. However, lymphocytes in such gut-associated lymphatic tissues as Peyer's patches and mesenteric lymph nodes were activated by the administration of (-)-matairesinol.

Affinity to the nicotinic acetylcholine receptor and insecticidal activity of chiral imidacloprid derivatives with a methylated imidazolidine ringHisashi Nishiwaki, Hikaru Nagaoka, Mituhiro Kuriyama, Satoshi Yamauchi, Yoshihiro Shuto, Bioscience, Biotechnology and Biochemistry, 75, 2011年05月16日, Four imidacloprid derivatives with an asymmetrically methylated imidazolidine ring were synthesized. Their affinity to the nicotinic acetylcholine receptor of housefly Musca domestica and insecticidal activity against the housefly were measured. The compound with a 5R-methylated imidazolidine ring demonstrated intrinsic activity comparable to that of the unsubstituted compound. Most of the compounds were synergized by oxygenase inhibitors.

Studies on the structure-activity relationship and mode of actions of neonicotinoid insecticidesHisashi Nishiwaki, Journal of Pesticide Science, 29, 2004年12月01日, The binding affinity of neonicotinoids for housefly head membranes was evaluated to elucidate the physicoehemical features of the compounds involved in the ligand-nicotinic acetylcholine receptor (nAChR) interactions. Both steric and electrostatic factors of the substituents on the aromatic and imidazolidine rings were found to influence the binding affinity. [ 14 C]Imidacloprid was employed to clarify the metabolism of imidacloprid in the flies. It was found that the compound was degraded and the metabolites were then excreted from the flies in a short period after administration. Agonist actions of neonicotinoids on nAChRs were evaluated to examine their relationships with the binding and insecticidal activities. High correlations were observed among these activities, suggesting that the channel opening of nAChRs resulting from the neonicotinoid binding is likely to cause the insecticidal actions.

Metabolism of imidacloprid in housefliesHisashi Nishiwakl, Kazuyuki Sato, Yoshiaki Nakagawa, Masahiro Miyashlta, Hisashi Miyagawa, Journal of Pesticide Science, 29, 2004年08月26日, Metabolism of imidacloprid in the housefly Musca domestica was investigated. After the injection of 14 C-labeled imidacloprid, radioactivity decreased to approximately 20% of the initial level within 24 hr. Most of the 14 C in the excreta as well as that in the insect body was accounted for by an olefin derivative of imidacloprid. The pre-application of piperonyl butoxide or propargyl propyl phenylphosphonate as a synergist suppressed the degradation of imidacloprid and delayed the excretion of insecticidal components from houseflies. These results suggested that the insecticidal activity of imidacloprid was affected by oxidative metabolic processes.

Purification and functional characterization of insecticidal sphingomyelinase C produced by Bacillus cereusHisashi Nishiwaki, Katsuhiko Ito, Katsuhiko Otsuki, Hiroyuki Yamamoto, Koichiro Komai, Kazuhiko Matsuda, Kazuhiko Matsuda, European Journal of Biochemistry, 271, 2004年02月01日, Bacillus cereus isolated from the larvae of Myrmeleon bore was found to secrete proteins that paralyze and kill German cockroaches, Blattela germanica, when injected. One of these active proteins was purified from the culture broth of B. cereus using anion-exchange and gel-filtration chromatography. The purified toxin, with a molecular mass of 34 kDa, was identified as sphingomyelinase C (EC 3.1.4.12) on the basis of its N-terminal and internal amino-acid sequences. A recombinant sphingomyelinase C expressed in Escherichia coli was as potent as the native protein in killing the cockroaches. Site-directed mutagenesis (His151Ala) that inactivated the sphingomyelinase activity also abolished the insecticidal activity, suggesting that the rapid insect toxicity of sphingomyelinase C results from its phospholipid-degrading activity.

Binding activity of substituted benzyl derivatives of chloronicotinyl insecticides to housefly-head membranes, and its relationship to insecticidal activity against the housefly Musca domesticaHisashi Nishiwaki, Yoshiaki Nakagawa, Yoshiaki Nakagawa, David Y. Takeda, Atsushi Okazawa, Miki Akamatsu, Hisashi Miyagawa, Tamio Ueno, Keiichiro Nishimura, Pest Management Science, 56, 2000年10月14日, Variously substituted benzyl derivatives of chloronlcotinyl insecticides were synthesized with a wide range of substituents including halogens, NO 2 , CN, CF 3 and small alkyl and alkoxy groups at the ortho, meta and para positions, as well as multiple-substituted benzyl analogues. Their binding activity to the α-bungarotoxin binding site in housefly (Musca domestica) head membrane preparations was measured. Among the compounds tested, the activity of the meta-CN derivative was the highest, being 20-100 times higher than those of imidacloprid, acetamiprid and nitenpyram. The synergized insecticidal activity against houseflies was also measured for selected compounds with the metabolic inhibitor, NIA16388 (propargyl propyl phenylphosphonate). For the nitromethylene analogues, including both benzyl and pyridylmethyl analogues, higher binding activity usually resulted in higher insecticidal activity. (C) 2000 Society of Chemical Industry.

Three-dimensional quantitative structure-activity relationship analysis of acyclic and cyclic chloronicotinyl insecticidesAtsushi Okazawa, Miki Akamatsu, Miki Akamatsu, Hisashi Nishiwaki, Yoshiaki Nakagawa, Hisashi Miyagawa, Keiichiro Nishimura, Tamio Ueno, Pest Management Science, 56, 2000年06月01日, The binding activity of chloronicotinyl insecticides, including acetamiprid, nitenpyram and related compounds, to the nicotinic acetylcholine receptors (nAChR) of houseflies was measured. These compounds were defined as 'acyclic' compounds. Variations in the binding activity were analysed using comparative molecular field analysis (CoMFA) which is a technique for the analysis of three-dimensional quantitative structure-activity relationships. The CoMFA results showed that steric interactions were more significant for the acyclic compounds than for imidacloprid and its derivatives (cyclic compounds). It was also shown that the acyclic compounds could bind to housefly-nAChR in a similar manner to the cyclic compounds, and that the electrostatic natures of the acyclic amino- and cyclic imdazolidine-moieties affected their binding activity. (C) 2000 Society of Chemical Industry.

Prediction of the binding mode of imidacloprid and related compounds to house-fly head acetylcholine receptors using three-dimensional QSAR analysisA. Okazawa, M. Akamatsu, A. Ohoka, H. Nishiwaki, W. J. Cho, Y. Nakagawa, K. Nishimura, T. Ueno, Pesticide Science, 54, 1998年01月01日, The binding activity of imidacloprid and related compounds to nicotinic acetylcholine receptors (nAChR) of house flies was measured by use of radioactive α-bungarotoxin as a ligand. Variations in the activity were examined three-dimensionally using comparative molecular field analysis (CoMFA). The CoMFA results suggest that one conformer among the four stable ones is active and provide support for one of the proposed binding models for this class of compound, in which the nitrogen atom of the pyridine ring and the nitrogen atom at the 1-position of the imidazolidine ring interact with the hydrogendonating and electron-rich sites of nAChR, respectively. The CoMFA field map showed that the nitroimino moiety and a portion of the imidazolidine ring were mainly surrounded by a sterically and electrostatically sensitive region of nAChR.